No abstract

Immature mice are highly susceptible to blastomycosis, which is similar to other mycoses and has parallels in humans. The murine susceptibility is noteworthy in that it persists beyond the development of resistance to other, nonfungal pathogens and the maturation of most immune functions. As the susceptibility to blastomycosis appeared to be related to an early event after infection, primary effector cell function was studied. We found that peritoneal inflammatory cells, enriched for neutrophils, from immature (3-week-old) mice killed nonphagocytizable Blastomyces dermatitidis cells less (25%) than did cells from mature (8-week) mice (70%) (P < 0.01), a defect intrinsic to the neutrophils. This correlated with an impaired immature cell oxidative burst. Killing of phagocytizable Candida albicans was not significantly different, 73 versus 87%. Thioglycolate-elicited cells were more impaired; killing of B. dermatitidis was insignificant, and killing of C. albicans was more impaired in immature (16% killing) than in mature (45%) cells (P < 0.02). Peripheral blood neutrophils from mature animals killed B. dermatitidis (41%) more than did those from immature animals (10%) (P < 0.02); C. albicans was killed efficiently by both. Resting or activated peritoneal macrophages from both types of animals showed no differences in B. dermatitidis killing. These results suggest that the susceptibility of immature mice is related at least in part to the depressed capacity of their neutrophils to kill B. dermatitidis.Previous studies from our laboratory have shown striking differences in the susceptibilities of immature and mature mice to blastomycosis (8). For example, for challenges via the pulmonary route, 5-week-old mice were 1,000-fold more susceptible than 9-week-old mice. This striking difference in susceptibility was not dependent on the route of challenge. Resistance developed progressively over age 3 to 10 weeks. Studies involving serial sacrifice of infected cohorts revealed that the infectionlimiting event in older mice, i.e., the interval before infectious burdens began to diverge in the two age groups, occurred within 4 days of challenge (8). This timing suggested that the difference in the age groups rested in differences in nonspecific immunity, e.g., activity of effector cells, rather than specific humoral or lymphocyte-mediated immunity, which would require more time for its expression. The studies reported here address the possible mechanism of the age-related differences in immunity, by studying effector cell function.